The macula, the area of the retina critical for central vision, is a unique feature of human and nonhuman primates. It contains two yellow carotenoid pigments, lutein and zeaxanthin, which are obtained from plant foods. These pigments are thought to protect the macula from age-related and light-induced degenerative changes by optical filtering of blue light and by their action as antioxidants. Retinal photoreceptors contain high levels of very polyunsaturated n-3 fatty acids which are important for normal retinal function but are particularly susceptible to oxidative damage. We are examining the interactive effects of dietary carotenoid depletion and n-3 fatty acid status on macular status in rhesus monkeys. From birth, 20 rhesus monkeys were fed semipurified diets containing all essential nutrients but no carotenoids. Eight received high levels and 13 received low levels of n-3 fatty acids as 18:3n-3 (8 vs. 0.3% of fatty acids), diets previously shown to produce a 6-fold difference in retinal levels of n-3 fatty acids. Macular integrity was evaluated with retinal fundus photographs and fluorescein angiograms and compared with results for age-matched monkeys fed standard stock diets. Serum carotenoids were measured by HPLC and macular pigment density by an in vivo photographic method, monochromatic reflectometry. In 6 other monkeys fed the same diets, macular morphology was examined by light and electron microscopy. Monkeys fed carotenoid-free diets had no measurable serum lutein or zeaxanthin, no detectable macular pigment and a significantly increased incidence of angiographic transmission defects (p<.01), indicating abnormalities in retinal pigment epithelial cells. Groups fed high and low levels of n-3 fatty acids did not differ. By electron microscopy some retinas, particularly in the low n-3 group, showed marked lipofuscin accumulation in the macular pigment epithelium. These results add to previous data suggesting that dietary carotenoids may protect the macula from degenerative changes. Angiography did not confirm a deleterious effect of retinal n-3 fatty acid depletion, as suggested by previous developmental studies, nor a protective effect, as suggested by studies of light-induced retinal damage. Carotenoid depleted monkeys provide a valuable model for examining the importance of these nutrients for macular health. FUNDING NIH DK-29930; The Foundation Fighting Blindness and Hoffmann-LaRoche PUBLICATIONS None